The effect of delta9-tetrahydrocannabinol on the conversion of [3H]trypotphan to 5-[3H] hydroxytryptamine in the mouse brain.

The effects of a 30-min pretreatment with varying doses of delta9-tetrahydrocannibinol (delta9-THC) on the synthesis of 5-[3H]hydroxytryptamine (5-[3H]HT) from an intravenous 10-min pulse of L-[3H]tryptophan ([3H]try) were measured in the mouse brain. We also determined the effects of delta9-THC on several parameters believed to influence the synthesis of brain 5-HT, including total and free plasma tryptophan and the high-affinity synaptosomal uptake of tryptophan. Delta9-THC was found to increase the amount of [3H]try accumulated by the brain as well as the amount of 5-[3H]HT synthesized. This effect was greater at intermediate doses than at the highest dose tested. However, delta9-THC was determined to have no effect on the actual rate of conversion of [3H]try into 5-[3H]HT at any dose tested. Delta9-THC had no effect on either plasma tyrosine ot free tryptophan levels. However, delta9-THC decreased total plasma tryptophan at low and intermediate doses, but had no effect at the highest dose tested. Synaptosomal uptake of [3H]try was unaffected by pretreatment with delta9-THC at any dose tested. These data suggest that delta9-THC increases the synthesis of 5-HT, not by altering the actual rate of conversion of tryptophan to 5-HT, but by altering, via an unknown mechanism, the quantity of tryptophan available for conversion to 5-HT.